chr3-46373906-C-T

Position:

chr3-46373906-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001394783.1(CCR5):c.1004C>T(p.Ala335Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,607,354 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 23 hom. )

Consequence

CCR5
NM_001394783.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.31

Variant links:

Genes affected

CCR5 (HGNC:1606): (C-C motif chemokine receptor 5) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]

CCR5 links:

CCR5AS (HGNC:54398): (CCR5 antisense RNA)

CCR5AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027053952).

BP6

Variant 3-46373906-C-T is Benign according to our data. Variant chr3-46373906-C-T is described in ClinVar as [Benign]. Clinvar id is 8187.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1618/152324) while in subpopulation AFR AF= 0.0361 (1501/41564). AF 95% confidence interval is 0.0346. There are 28 homozygotes in gnomad4. There are 727 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1618 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCR5	NM_001394783.1 linkuse as main transcript	c.1004C>T	p.Ala335Val	missense_variant	2/2	ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.1 linkuse as main transcript	n.392-2489G>A		intron_variant, non_coding_transcript_variant
CCR5	NM_000579.4 linkuse as main transcript	c.1004C>T	p.Ala335Val	missense_variant	3/3		NP_000570.1
CCR5	NM_001100168.2 linkuse as main transcript	c.1004C>T	p.Ala335Val	missense_variant	3/3		NP_001093638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCR5	ENST00000292303.5 linkuse as main transcript	c.1004C>T	p.Ala335Val	missense_variant	2/2	1	NM_001394783.1	ENSP00000292303	P1
CCR5AS	ENST00000701879.1 linkuse as main transcript	n.174-2489G>A		intron_variant, non_coding_transcript_variant
CCR5	ENST00000445772.1 linkuse as main transcript	c.1004C>T	p.Ala335Val	missense_variant	1/1			ENSP00000404881	P1
CCR5AS	ENST00000451485.2 linkuse as main transcript	n.392-2489G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1613

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00291

AC:

711

AN:

244606

Hom.:

AF XY:

0.00220

AC XY:

290

AN XY:

131888

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.000212

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000272

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.00115

AC:

1668

AN:

1455030

Hom.:

Cov.:

AF XY:

0.000978

AC XY:

707

AN XY:

723114

show subpopulations

Gnomad4 AFR exome

AF:

0.0385

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.000234

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000200

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000722

Gnomad4 OTH exome

AF:

0.00289

GnomAD4 genome

AF:

0.0106

AC:

1618

AN:

152324

Hom.:

Cov.:

AF XY:

0.00976

AC XY:

727

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0361

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.0123

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0352

AC:

155

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00338

AC:

411

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCR5 POLYMORPHISM, AFRICAN-AMERICAN

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 01, 1997

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0060

DANN

Benign

0.88

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.52

.;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0050

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.025

Sift

Benign

0.46

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0

B;B

Vest4

0.020

MVP

0.20

ClinPred

0.0078

GERP RS

-11

Varity_R

0.021

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over